Toxic and Side Effects

Unsuccessful development is often due to toxicological problems which remain unpublished. Hence little is publicly known about the toxicity of aldose reductase inhibitors. 

The presence of aldose reductase in many tissues, which may not be involved in diabetic complications, makes unwanted effects likely, although isozymic differences in the enzyme in different tissues may be possible. Since aldose reductase inhibitors are not yet regularly used and since the effects of long-term inhibition of aldose reductase are not yet known, knowledge on possible unwanted effects is scarce. Information on side effects is therefore based only on individual reports. 

The absence of side effects in a 1-year clinical trial with ponalrestat was reported by Ziegler et al. (1991), but in this study no therapeutic efficacy was seen A 6-month study with ponalrestat to elucidate the effects on kidney function was also free from side effects (Pedersen et al., 1991). Dizziness, possibly based on a blood pressure-lowering effect, was reported for tolrestat. In addition, hepatocyte lesion accompanied by changes in hepatic parameters within the first 3-6 months of treatment was seen (Ryder et al., 1987). For sorbinil, significant hypersensitivity reactions have been reported (Sarges, 1989). 

No report on drug interaction exists as yet. Possible interactions based on plasma protein binding are discussed in the pharmacokinetic section. 

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Noting that diabetes, the target disease, is a chronic condition that requires long-term treatment, the district court concluded that researchers would have been dissuaded from selecting compound (2) as a lead compound because of its suboptimal toxicity and side-effect profile [35]. 

Product quality, purity and consistency are critically important in the pharmaceutical sector, applying to all stages of the supply chain and final dosed product. The human body is an exceptionally complex system and the full effect of a pharmaceutical product, consisting of the API, impurities and formulation components, is impossible to predict from first principles. The industry relies on rigorous clinical trials to assess drug efficacy, toxicity and side effect profiles. 

Anticonvulsants. Scattered case reports suggest that carbamazepine (Tegretol) and valproic acid (Depakote, Depakene) may be helpful in the treatment of panic disorder. This has yet to be verified in systematic studies. Furthermore, because these anticonvulsants are hindered by toxicity and side effect concerns (cf. Chapter 3), they should only be considered if other better studied and more tolerable treatment options have failed. 

Reduction in the toxicity and side effects due to the greater specificity of action of the isomer with the relevant biological processes. 

Enzyme Induction (CYP3A4) and Drug Design 1119 Tab. 8.4 Clinical toxicities and side-effects of P4503A4 inducers. 

In classical texts, three groups of herbs are identified which are forbidden to be used together, otherwise toxicity and side effects may occur. 

Nanoparticles have numerous applications in the chemical, food, pharmaceutical, biomedical and semiconductor industries. For example, nanoparticles as drug carriers can increase drug efficacy, and can reduce toxicity and side effect after parenteral administration (Feng et al., 2002). Nanoparticles used for industrial applications should have desirable physical properties, including appropriate size, surface charge, surface area, porosity and mechanical strength. The functionality of... 

Despite their important specificity, toxicity and side effects similar to those of the standard cytotoxic chemotherapeutic approaches can also occur with signal transduction inhibitors. 

Anisodine is a natural TTA that represents a derivative of the scopolamine structure mono-hydroxylated at the tropic acid moiety (Fig. 1). Similar to anisodamine it was extracted from Chinese herb Anisodus tanguticus (Maxim.) Pascher and also exhibits al-AR blocking properties and non-specific anticholinergic effects. Accordingly, in China anisodine is used for the therapy of the same indications as described for anisodamine, most often to treat transmissible shock. Toxicity and side effects of anisodine are smaller than those for atropine, scopolamine and anisodamine [5],... 

Invention Significance Significant toxicity and side effects are often... 

The inhibition of tumorigenesis by curcumin may also be mediated through modulation of a signal transduction pathway(s) associated with tumor promotion. Preclinical efficacy studies and the lack of toxicity and side effects, as well as the... 

Pooga, M., Elmquist, A., and Langel, U. (2002) Toxicity and side effects of cell-penetrating peptides, in Cell Penetrating Peptides, Processes and Applications (Langel, U., ed.), CRC Press, Boca Raton, London, New York, Washington, pp. 245-261. 

Chen YZ, Ung CY. Prediction of potential toxicity and side effect protein targets of a small molecule by a ligand-protein inverse docking approach. J. Mol. Graph Model 2001 20 199-218. 

Use of formulation techniques can improve the bioavailability and/or minimize the toxicity and side effects of drugs. Factors to consider include those that impact on solubility and dissolution rates, chemical and enzymatic stability, and absorption capability. 

Zaffaroni, A. Special requirements for hormone releasing intrauterine devices. Meeting on Pharmacological Models to Assess Toxicity and Side Effects of Fertility Regulating Agents, Geneva, 1974 423-434. 

Finn AL. Toxicity and side effects of ondansetron. Semin Oncol 1992 19(4 Suppl 10) 53-60. 

Dillman RO, Beauregard JC, Halpern SE, Clutter M. Toxicities and side effects associated with intravenous infusions of murine monoclonal antibodies. J Biol Response Mod 1986 5(l) 73-84. 

Monoclonal antibodies can vary tremendously in terms of isotype, construction (animal derived, chimeric, humanized, bound to toxin), ability to activate complement, binding avidity, target specificity, and whether it binds and blocks or binds and activates the receptor. Monoclonal antibodies may be directed toward soluble or membrane bound receptors or receptor ligands, tumor antigens, growth factor or their receptors. Therefore toxicity and side effects are equally variable [68]. 

Prodrugs masking drug toxicity and side-effects... 

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